Treatment of advanced gastrointestinal stromal tumors in patients over 75 years old: clinical and pharmacological implications

Target Oncol. 2013 Dec;8(4):295-300. doi: 10.1007/s11523-012-0243-8. Epub 2012 Dec 21.

Abstract

Data about the patterns of care and the specific outcome of elderly patients with advanced gastrointestinal stromal tumors (GISTs) are almost nonexistent. Between 2001 and 2009, 44 patients ≥75 years old with advanced GISTs started first-line imatinib (400 mg/day) in seven participating institutions. Clinical data were collected by reviewing medical records and were entered in a comprehensive database. During the same period, 160 patients with advanced GIST (136 patients <75 years old, 24 patients ≥75 years old) had access to an imatinib blood level testing program. Imatinib plasma concentration (patient dose 400 mg/day) tests were centralized in a single laboratory. Median age was 78 years old (range 75-86). Thirty-six patients (82 %) experienced at least one adverse event (Table 2). Drug-related adverse events were mainly of grades 1 and 2 and were medically manageable. Permanent dose reduction (200-300 mg/day) was required for 20 patients (45.5 %) and was significantly more frequent for patients with performance status (PS) ≥2: 33.5 versus 8.5 %, p = 0.04. Eight patients (18 %) required imatinib interruption for intolerance. Median PFS was 34.4 months (95 % CI 11.5-57.4) (Fig. 1). Median overall survival (OS) was 50.3 months (95 % CI 37-63.5). Performance status <2 was the sole pre-therapeutic factor associated with improved OS. No correlation was found between comorbidities and tolerance or outcome. Imatinib trough plasma concentrations increase with age, although this correlation did not reach statistical significance. First-line imatinib is a feasible and effective treatment in patients with advanced GISTs ≥75 years. Aging seems to have only a moderate impact on imatinib pharmacokinetics. Overall survival is similar to that of younger patients. Comorbidities did not result in increased incidence of toxicity. Careful follow-up regarding tolerance issues should be considered in elderly patients with poor PS.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Benzamides / blood
  • Benzamides / pharmacokinetics
  • Benzamides / therapeutic use*
  • Female
  • Gastrointestinal Stromal Tumors / blood
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / metabolism
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Imatinib Mesylate
  • Male
  • Piperazines / blood
  • Piperazines / pharmacokinetics
  • Piperazines / therapeutic use*
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / therapeutic use*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate